Description:
This phase I trial studies the side effects and the best dose of vosaroxin when given
together with azacitidine in treating patients with myelodysplastic syndromes. Drugs used in
chemotherapy, such as vosaroxin and azacitidine, work in different ways to stop the growth of
cancer cells, either by killing the cells or by stopping them from dividing.
Title
- Brief Title: Vosaroxin and Azacitidine in Treating Patients With Myelodysplastic Syndromes
- Official Title: A Phase I Study of Vosaroxin Plus Azacitidine for Patients With Myelodysplastic Syndrome
Clinical Trial IDs
- ORG STUDY ID:
201309091
- NCT ID:
NCT01913951
Conditions
- Myelodysplastic Syndromes
Interventions
Drug | Synonyms | Arms |
---|
vosaroxin | voreloxin | Treatment (vosaroxin, azacitidine) |
Azacitidine | Vidaza, Ladakamycin | Treatment (vosaroxin, azacitidine) |
Purpose
This phase I trial studies the side effects and the best dose of vosaroxin when given
together with azacitidine in treating patients with myelodysplastic syndromes. Drugs used in
chemotherapy, such as vosaroxin and azacitidine, work in different ways to stop the growth of
cancer cells, either by killing the cells or by stopping them from dividing.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (vosaroxin, azacitidine) | Experimental | Patients receive vosaroxin IV over 10 minutes on days 1 and 4 and azacitidine SC or IV over 15 minutes on days 1-7. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. | |
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of myelodysplastic syndrome and one of the following:
- Cytopenias requiring red blood cell and/or platelet transfusions or neutropenia
(ANC <1 X109/L)
- IPSS score of INT-1 or higher at screening
- MDS with excess blasts in transformation as defined by FAB criteria (20-29% bone
marrow blasts) or
- Chronic myelomonocytic leukemia
- Age ≥18 years old
- Adequate renal and hepatic function defined as all of the following:
- total bilirubin ≤ 2.0 mg/dl, except in cases of Gilbert's disease;
- AST and ALT ≤2.5 institutional ULN;
- serum creatinine within normal institutional limits or estimated creatinine
clearance ≥60 mL/min/1.73 m2 by the Cockcroft-Gault equation
- ECOG performance status ≤2
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
- Females must be surgically or biologically sterile or postmenopausal or if of
childbearing potential, must agree to use an adequate method of contraception during
the study until 30 days after the last treatment. Males must be surgically or
biologically sterile or agree to use an adequate method of contraception during the
study until 30 days after the last treatment. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she must inform her
treating physician immediately.
- Patients may have received up to 3 prior cycles of hypomethylator therapy (i.e.
decitabine or azacitidine) prior to enrollment and may have received supportive care
measures (growth factors, erythropoietin stimulating agents, transfusion, etc.
- Either enrolled in HRPO# 201011766 ("Tissue Acquisition for Analysis of Genetic
Progression Factors in Hematologic Diseases"), which facilitates collection of blood,
bone marrow, and skin for correlative studies, or consents to collection of blood,
bone marrow, and skin as part of this protocol.
Exclusion Criteria:
- Prior treatment with four or more cycles of hypomethylator therapy.
- Receiving concomitant chemotherapy, radiation therapy, or immunotherapy during the
duration of treatment on protocol.
- Known seropositivity for or active viral infection with human immunodeficiency virus
(HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients who are
seropositive because of hepatitis B virus vaccine are eligible. Patients who are
seropositive for HCV, but have a negative viral load are also eligible. Documentation
that the patients have completed a course of therapy for HCV is required and will be
obtained.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Pregnant and/or breastfeeding.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | MTD of vosaroxin in combination with azacitidine |
Time Frame: | 28 days |
Safety Issue: | |
Description: | Defined as the highest dose of vosaroxin that results in a DLT in =< 1 of 6 patients graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0 |
Secondary Outcome Measures
Measure: | Best response (including hematologic improvement) |
Time Frame: | At 3 cycles |
Safety Issue: | |
Description: | According to the modified IWG criteria. Summarized as proportion with 95% confidence intervals. |
Measure: | Best overall response |
Time Frame: | Up to 7 months |
Safety Issue: | |
Description: | According to the modified IWG criteria. Summarized as proportion with 95% confidence intervals |
Measure: | Incidence of adverse events |
Time Frame: | Up to 7 months |
Safety Issue: | |
Description: | Graded according to NCI CTCAE v. 4.0. summarized by grade, type and patient. |
Measure: | Time to response |
Time Frame: | Up to 7 months |
Safety Issue: | |
Description: | According to the modified IWG criteria. Described using Kaplan-Meier models to plot these endpoints and estimate median times with a 95% confidence interval. |
Measure: | Event-free survival |
Time Frame: | up to 5 years |
Safety Issue: | |
Description: | From the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause. Described using Kaplan-Meier models to plot these endpoints and estimate median times with a 95% confidence interval. |
Measure: | Progression-free survival (PFS) |
Time Frame: | up to 5 years |
Safety Issue: | |
Description: | From the date of first dose of study drug to disease progression or death from MDS. Described using Kaplan-Meier models to plot these endpoints and estimate median times with a 95% confidence interval. |
Measure: | Disease-free survival (DFS) |
Time Frame: | up to 5 years |
Safety Issue: | |
Description: | From the date of first documentation of a complete remission (CR) to date of relapse. Described using Kaplan-Meier models to plot these endpoints and estimate median times with a 95% confidence interval. |
Measure: | Overall survival (OS) |
Time Frame: | up to 5 years |
Safety Issue: | |
Description: | Date of first dose of study drug to the date of death from any cause. Described using Kaplan-Meier models to plot these endpoints and estimate median times with a 95% confidence interval. |
Measure: | Biomarkers of response to vosaroxin and azacitidine therapy |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | Serial estimate of biomarker expression will be plotted and summarized over time using means and standard deviations, possibly on a log scale |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Washington University School of Medicine |
Last Updated
June 16, 2021